crossing96/oncoscreening huggingface dataset:
Potential therapeutic effects of N-butylidenephthalide from Radix Angelica Sinensis (Danggui) in human bladder cancer cells.	BACKGROUND: N-butylidenephthalide (BP) isolated from Radix Angelica Sinensis (Danggui) exhibits anti-tumorigenic effect in various cancer cells both in vivo and in vitro. The effect of BP in bladder cancer treatment is still unclear and worth for further investigate. METHODS: Changes of patients with bladder cancer after Angelica Sinensis exposure were evaluated by analysis of Taiwan's National Health Insurance Research Database (NHIRD) database. The anti-proliferative effect of BP on human bladder cancer cells was investigated and their cell cycle profiles after BP treatment were determined by flow cytometry. BP-induced apoptosis was demonstrated by Annexin V-FITC staining and TUNEL assay, while the expressions of apoptosis-related proteins were determined by western blot. The migration inhibitory effect of BP on human bladder cancer cells were shown by trans-well and wound healing assays. Tumor model in NOD-SCID mice were induced by injection of BFTC human bladder cancer cells. RESULTS: The correlation of taking Angelica sinensis and the incidence of bladder cancer in NHIRD imply that this herbal product is worth for further investigation. BP caused bladder cancer cell death in a time- and dose- dependent manner and induced apoptosis via the activation of caspase-9 and caspase-3. BP also suppressed the migration of bladder cancer cells as revealed by the trans-well and wound healing assays. Up-regulation of E-cadherin and down-regulation of N-cadherin were evidenced by real-time RT-PCR analysis after BP treatment in vitro. Besides, in combination with BP, the sensitivity of these bladder cancer cells to cisplatin increased significantly. BP also suppressed BFTC xenograft tumor growth, and caused 44.2% reduction of tumor volume after treatment for 26 days. CONCLUSIONS: BP caused bladder cancer cell death through activation of mitochondria-intrinsic pathway. BP also suppressed the migration and invasion of these cells, probably by modulating EMT-related genes. Furthermore, combination therapy of BP with a lower dose of cisplatin significantly inhibited the growth of these bladder cancer cell lines. The incidence of bladder cancer decreased in patients who were exposed to Angelica sinensis, suggesting that BP could serve as a potential adjuvant in bladder cancer therapy regimen.	bladder
FGFR inhibitor BGJ398 and HDAC inhibitor OBP-801 synergistically inhibit cell growth and induce apoptosis in bladder cancer cells.	In advanced bladder cancer, cisplatin-based chemotherapy has been the standard treatment for many years, but there are many problems in terms of side-effects. Recently, a number of clinical trials using molecular-targeted agents have been conducted, and new therapies are expected that could replace conventional cytotoxic chemotherapy. We herein report that concurrent treatment with fibroblast growth factor receptor (FGFR) inhibitor BGJ398 and the novel histone deacetylase (HDAC) inhibitor OBP-801/YM753/spiruchostatin A synergistically inhibited cell growth and markedly induced apoptosis in high-grade bladder cancer cells. This combination activated caspase-3, -8 and -9, and the pan-caspase inhibitor zVAD-fmk significantly reduced the apoptotic response to the combined treatment. The combination upregulated the expression of Bim, one of the pro-apoptotic molecules. In the present study, Bim siRNA efficiently reduced apoptosis induced by the co-treatment of BGJ398 and OBP-801. Therefore, the apoptosis induced by the combination was shown to be at least partially dependent on Bim. Taken together, these results suggest that the combination of BGJ398 and OBP-801 is a novel high potential therapeutic strategy for muscle-invasive bladder cancer.	bladder
Donor-derived, metastatic urothelial cancer after kidney transplantation associated with a potentially oncogenic BK polyomavirus.	BK polyomavirus has been linked to urothelial carcinoma in immunosuppressed patients. Here, we performed comprehensive genomic analysis of a BK polyomavirus-associated, metachronous, multifocal and metastatic micropapillary urothelial cancer in a kidney transplant recipient. Dissecting cancer heterogeneity by sorting technologies prior to array-comparative genomic hybridization followed by short tandem repeat analysis revealed that the metastatic urothelial cancer was of donor origin (4-year-old male). The top 50 cancer-associated genes showed no key driver mutations as assessed by next-generation sequencing. Whole genome sequencing and BK polyomavirus-specific amplification provided evidence for episomal and subgenomic chromosomally integrated BK polyomavirus genomes, which carried the same unique 17-bp deletion signature in the viral non-coding control region (NCCR). Whereas no role in oncogenesis could be attributed to the host gene integration in chromosome 1, the 17-bp deletion in the NCCR increased early viral gene expression, but decreased viral replication capacity. Consequently, urothelial cells were exposed to high levels of the transforming BK polyomavirus early proteins large tumour antigen and small tumour antigen from episomal and integrated gene expression. Surgery combined with discontinuation of immunosuppression resulted in complete remission, but sacrificed the renal transplant. Thus, this report links, for the first time, BK polyomavirus NCCR rearrangements with oncogenic transformation in urothelial cancer in immunosuppressed patients. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.	bladder
The Current Status and Future Role of the Phosphoinositide 3 Kinase/AKT Signaling Pathway in Urothelial Cancer: An Old Pathway in the New Immunotherapy Era.	The phosphoinositide 3 kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway is a well studied signaling pathway that regulates diverse cellular functions including proliferation, metabolism, and transcription. Aberrant activation of this pathway has been implicated in multiple cancers. Genomic studies have shown that activating mutations in oncogenes as well as inactivating mutations in tumor suppressor genes are present across a variety of malignancies, including urothelial carcinoma. In bladder cancer, up to 40% of tumors exhibit constitutive activation of the PI3K/AKT/mTOR pathway. Current treatments for non-muscle-invasive disease confer a 5-year cancer-specific survival rate as high as 90%. However, patients with muscle-invasive, recurrent, or metastatic disease have a poor prognosis. Although the introduction of immune checkpoint inhibitors is certainly changing the therapeutic landscape and is a great addition to the platinum-based therapy that was the standard of care for the past 3 decades, it is anticipated that a great number of patients would fail to respond or their disease would progress with either chemotherapy or immunotherapy. Therefore, the use of agents that target members of the PI3K/AKT/mTOR pathway represent an attractive, alternative therapeutic strategy for patients with advanced urothelial carcinoma. In this review we describe the pathway, with a focus on the rationale for targeting the PI3K/AKT/mTOR pathway in patients with advanced urothelial carcinoma and considers the challenges that we face from the current clinical trials. Novel agents such as PI3K inhibitors and microRNA inhibitors that target this pathway might lead to durable responses especially when used in combination with chemotherapy or immune checkpoint inhibitors, however, toxicity remains an obstacle. Finally, in this review we discuss the importance of developing biomarkers to help select appropriate patients and identify optimal treatment options.	bladder
Nephrogenic Adenoma Complicating Renal Transplantation: A Case Report and Discussion.	Nephrogenic adenoma (NA) is a benign adenomatous lesion of the urinary tract. Long considered to be a rare phenomenon, case series from the renal transplant population suggest that it may be much more common within this group. Although NA is considered to be a lesion with low premalignant potential, hematuria, lower urinary tract symptoms, and recurrent urinary tract infections (UTIs) are frequently observed in the context of NA. Furthermore, after resection of NA, lesion recurrence and persistent symptoms are frequently observed. Here we present the case of a 69-year-old male renal transplant recipient with NA and associated recurrent UTIs despite cystoscopic resection of the primary lesion. This case is illustrative of the clinical impact of NA and the need for ongoing work into the development of strategies to manage this problematic phenomenon.	bladder
[The relationship between tumor recurrence and polymorphisms of hGPX1 and NRAMP1 in superficial bladder cancer patients: a meta-analysis].	INTRODUCTION: Previous studies about the relationship between tumor recurrence and NRAMP1 and HGPX1 gene polymorphism in patients with non-muscle-invasive bladder cancer (NMIBC) showed inconsistent results. METHODS: We conducted a systematic review of the literature on the basis of data from PubMed and China National Knowledge Infrastructure. According to the predefined selection criteria, the eligibility criteria for the studies found in the literature were assessed by two independent authors. The basic characteristics of the included studies and of data relevant to the meta-analysis were extracted. Patients? survival without recurrence was selected as the measure of effect of meta-analysis. RESULTS: Four publications were retained. Three studies evaluated the NRAMP1 D534N and three the hGPX1 Pro168Leu. Depending on the association between NRAMP1 D534N and tumor recurrence, the meta-analysis revealed no significant heterogeneity and the combined effect was 3.28 [1.77, 6.11]. Depending on the association between hGPX1 Pro198Leu and tumor recurrence, the meta-analysis showed significant heterogeneity and the combined effect was 1.12 [0.45, 2.77]. Publication bias was uncertain, due to the limited number of included studies.The instability of the combined effects was reported. CONCLUSION: Very little data are available on the association between tumor recurrence and NRAMP1 D534N and hGPX1 Pro168Leu poolymorphisms in patients with NMIBC. The NRAMP1 D534N could increase the risk of recurrence, but hGPX1 Pro168Leu effect is not clear. A more thorough investigation should be conducted on a larger sample size in order to better explain this phenomenon.	bladder
miR34a/GOLPH3 Axis abrogates Urothelial Bladder Cancer Chemoresistance via Reduced Cancer Stemness.	Rationale: Chemoresistance and subsequent recurrence of human urothelial bladder cancer (UBC) is partially driven by a subpopulation of tumor initiating cells, namely cancer stem cells (CSCs). However, the underlying molecular mechanism in chemotherapy-induced CSCs enrichment and following chemoresistance and recurrence remains largely unclear. Methods: Gemcitabine and cisplatin (GC) chemoresistant cell lines (T24 GC 3(rd) and 5637 GC 3(rd) cells) and the chemo-sensitive UBC cell lines T24 and 5637 were established in vivo for the investigation of acquired resistance mechanisms. The role of miR34a/GOLPH3 axis in regulating UBC chemoresistance and recurrence was evaluated in cell and animal models. The expression levels of miR34a/GOLPH3 axis and CSCs markers were assayed in specimens of UBC. The association of GOLPH3 with clinicopathologic features and prognosis was analysed. Results: RT-PCR and western blotting confirmed that the expression levels of miR34a were decreased and GOLPH3 were increased in GC chemoresistant UBC cell lines. Downregulation of miR34a resulted in the overexpression of GOLPH3, which is a target gene of miR34a confirmed by luciferase experiment. The ectopic expression of miR34a decreased the stem cell properties of chemoresistant UBC cells and re-sensitized these cells to GC treatment in vitro and in vivo. Moreover, miR34a/GOLPH3 axis has obvious clinical relevance with prognosis and recurrence in human UBC patients with standard GC chemotherapy. Conclusion: Our results suggest that miR34a/GOLPH3 axis exert key role in CSCs involved UBC drug resistance and recurrence and warrant further development as a promising therapeutic approach in treating drug-resistant UBC.	bladder
[Intravesical microwave thermo-chemotherapy for the treatment of non-invasive bladder cancer].	Non-invasive urothelial carcinoma of the bladder is known for its significant rate of recurrence after transurethral resection (TURB) even after adjuvant intravesical chemotherapy or immunoprophylaxis. Therefore, new and more effective approaches for the management of non-invasive bladder tumors have been developed and are progressively introduced in clinical practice. Recently, the endovesical administration of a combined regimen using a cytostatic agent and microwave-induced hyperthermia appears to be highly efficient and possibly superior to intravesical chemotherapy alone for none invasive bladder cancer.	bladder
Preoperative chronic kidney disease is predictive of oncological outcome of radical cystectomy for bladder cancer.	PURPOSE: To evaluate the impact of preoperative chronic kidney disease (CKD) on oncological outcomes after radical cystectomy (RC) for bladder cancer. METHODS: We reviewed the medical records of patients with urothelial bladder carcinoma who underwent RC with curative intent at seven hospitals between 1990 and 2013. After excluding patients with a history of upper urinary tract urothelial cancer or neoadjuvant chemotherapy, we analyzed 594 cases for the study. Preoperative estimated glomerular filtration rate (eGFR) was calculated using the three-variable Japanese equation for GFR estimation from serum creatinine level and age. Patients were divided into four groups of different CKD stages based on eGFR values (mL/min/1.73 m(2)), i.e., ≥ 60 (CKD stages G1-2), 45-60 (G3a), 30-45 (G3b), and < 30 (G4-5). Survival was estimated using the Kaplan-Meier method. Univariate and multivariate Cox proportional hazards regression analyses addressed survivals after RC. RESULTS: Median age of patients was 67 years. Patients were classified into CKD stages: G1-2 (n = 388; 65.3%), G3a (n = 122; 20.5%), G3b (n = 51; 8.6%), and G4-5 (n = 33; 5.6%). During a median follow-up of 4.0 years, 200 and 164 patients showed cancer progression and died of bladder cancer, with the 5-year progression-free survival (PFS) and cancer-specific survival (CSS) of 64.9 and 70.2%, respectively. On multivariate analyses, CKD stages of G3b or greater, advanced pT stage, lymph node metastasis, and positive lymphovascular invasion were independent poor prognostic factors for PFS and CSS. CONCLUSIONS: We demonstrated that the advanced preoperative CKD stage was significantly associated with poor oncological outcomes of the bladder cancer after RC.	bladder
Is the open cystectomy era over? An update on the available evidence.	In 2018, robot-assisted radical cystectomy will enter its 15th year. In an era where an effort is being made to standardize complication reporting and videos of the procedure are readily available, it is inevitable and justified that like everything novel, robot-assisted radical cystectomy should be scrutinized against the gold standard, open radical cystectomy. The present comparison is focused on several parameters: oncological, functional and complication outcomes, and direct and indirect costs. Meta-analysis and prospective randomized trials comparing robot-assisted radical cystectomy versus open radical cystectomy have been published, showing an oncological equivalence and in some cases an advantage of robot-assisted radical cystectomy in terms of postoperative morbidity. In the present review, we attempt to update the available knowledge on this debate and discuss the limitations of the current evidence that prevent us from drawing safe conclusions.	bladder
TM4SF1 regulates apoptosis, cell cycle and ROS metabolism via the PPARγ-SIRT1 feedback loop in human bladder cancer cells.	Transmembrane-4-L-Six-Family-1 (TM4SF1) is a member of the L6 family and functions as a signal transducer to regulate cell development, growth and motility. Here we show that TM4SF1 is strongly upregulated in human muscle invasive bladder cancer (MIBC) tissues, corroborating the bioinformatical results of transcriptome analysis. Moreover, tissue microarray (TMA) shows significant correlations (p < 0.05) between high expression of TM4SF1 and T stage, TNM stage, lymph node metastasis status and survival rate of MIBC patients, indicating a positive association between TM4SF1 expression and poorer prognosis. Furthermore, in vitro and in vivo studies indicate that the proliferation of human bladder cancer (BCa) cells is significantly suppressed by knockdown of TM4SF1 (p < 0.05). Functionally, the reduction of TM4SF1 could induce cell cycle arrest and apoptosis possibly via the upregulation of reactive oxygen species (ROS) in BCa cells. In addition, these observations could be recovered by treatment with GW9662 (antagonist of PPARγ) and resveratrol (activator of SIRT1). Taken together, our results suggest that high expression of TM4SF1 predicts poor prognosis of MIBC.	bladder
[Bladder cancer in neurogenic patients: A retrospective study of management and follow-up].	INTRODUCTION: The prevalence of bladder cancer (BC) in neurological patients seems to be similar to that of the general population. However, they are more aggressive with a higher rate of muscle-invasive forms and squamous cells carcinomas. The aim of the current study was to report etiologies, management and outcomes of BC in neurological population. MATERIAL AND METHOD: Were enrolled all neurological patients with a BC diagnosed between 2004 and 2017. The following data were retrospectively reported: age, gender, duration of the disease, mode of discovery, histological type, treatment and outcomes. RESULTS: In total, 27 patients were included: 11 spinal cord injuries, 7 Parkinson's disease, 5 multiple sclerosis, 3 head trauma, 3 brain strokes, 2 cerebral palsies and 1 spina bifida. The histological subtypes were as follows: 22 transitional cells carcinomas, 4 squamous cell carcinomas (SCC), one mucinous adenocarcinoma, one sarcomatoid and one neuroendocrine with 19 high-grade tumors and 15 muscle-invasive bladder cancer. Seven patients (26%) were diagnosed before 15 years history of neurogenic bladder. The mean follow-up was 14 months (1-210 months). Eight deaths were observed, with 5 related to bladder cancer. In our study, smoking habits, voiding mode, lithiasis or infection histories were not related with a more aggressive pattern, such as SCC. CONCLUSION: The high rate of muscle-invasive bladder cancer and aggressive patterns justify neuro-urological follow-up, even before 15 years of neurogenic bladder. LEVEL OF EVIDENCE: 4.	bladder
Can bladder preservation therapy come to the center stage?	Decision-making in urological cancer care requires a multidisciplinary approach for refinement, but its impact on urothelial carcinoma of the bladder has not been fully addressed for the past three decades, except for the latest immunological checkpoint inhibitor approved by the U.S. Food and Drug Administration for metastatic muscle-invasive bladder cancer that is resistant to platinum-based chemotherapy. For the time being, radical cystectomy is the gold standard of curative therapy for muscle-invasive bladder cancer. Trimodal therapy that combines chemotherapy for the purpose of radiation sensitization, external beam radiotherapy and transurethral resection of bladder tumor has emerged as a potential alternative treatment option that preserves the bladder. In lack of randomized studies for bladder preservation therapy compared with surgery, the principles of management of urothelial carcinoma of the bladder have evolved in recent times, with an emphasis on bladder preservation. A number of bladder preservation techniques are available to the surgeon; however, appropriately selected patients with muscle-invasive bladder cancer should be offered the opportunity to discuss various treatment options, including organ-sparing trimodal therapy. The aim of the present study was to compare the primary outcomes of the available treatment methods and identify the sources of variance among studies. A review of various bladder preservation techniques in vogue for the management of urothelial carcinoma of the bladder is discussed.	bladder
Secondary Malignancies of the Bladder: Avoiding the Diagnostic Pitfall.	Although rare, secondary tumors of the bladder can present a diagnostic dilemma to pathologists considering a differential diagnosis of primary bladder cancer. We investigated the clinicopathologic and imaging characteristics of metastatic tumors to the bladder. We retrospectively reviewed the surgical pathology databases from 2 sites from 2013 to 2016, identifying 66 cases of secondary bladder tumors. Clinical, pathologic, and imaging findings were reviewed. Mean age at diagnosis was 63 years (range = 25-87). Females had a significantly higher proportion (44/66, 66.7%) of secondary bladder tumors compared with males (22/66, 33.3%; P = .007). In total, 56/66 (84.8%) patients had a clinical history of an in situ or invasive malignancy in another organ, and 54/66 (81.8%) patients had imaging supporting a metastatic tumor. Only 2/66 (3.0%) patients had a prior history of urothelial carcinoma. In total, 4/66 (6.1%) cases (all females) were originally misdiagnosed as primary bladder malignancies and were corrected after clinicoradiologic correlation. Overall, colorectal origin was most common (15/66, 22.7%), followed by cervical and ovarian primaries (10/66, 15.2% each). Cervical and ovarian origins predominated in the female cohort (10/44, 22.7% each), followed by endometrial (8/44, 18.2%). Colorectal and prostate primaries were the most common among males (10/22, 45.5%, and 7/22, 31.8%, respectively). Secondary bladder tumors can mimic urothelial carcinomas. In our cohort, gynecological, colorectal, and prostatic origins were most common. Clinical history, imaging, and immunohistochemical studies can be useful in avoiding this diagnostic pitfall.	bladder
Microcystic transitional cell carcinoma: a rare tumor of the urinary bladder.	Microcystic urothelial carcinoma is a rare variant of invasive transitional cell carcinoma recognized by the WHO classification. It is characterized by its deceptively benign appearance. The clinical course of this uncommon variety of carcinoma is not well known and their histological and immunohistological features are not well defined. We report a case of a 37-year-old man with a microcystic transitional cell carcinoma of the urinary bladder. He was diagnosed 4 years ago with cystitis glandularis lesions and nephrogenic adenoma. Through this observation we will try to define the clinical and pathological features of this uncommon tumor which must be differentiated from a number of proliferative lesions of the urothelium. The poor prognosis and aggressiveness of this tumor seems to be related to a higher stage and grade at diagnosis.	bladder